Cormier V, Rotig A, Tardieu M, Colonna M, Saudubray J M, Munnich A
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-12, Hôpital des Enfants-Malades, Paris, France.
Am J Hum Genet. 1991 Apr;48(4):643-8.
Multiple deletions of the mitochondrial genome were found in a family in which the proband had ataxia and ketoacidotic comas. A progressive multiorgan involvement appeared in the course of the disease, and histopathological investigation demonstrated mitochondrial myopathy features with ragged red fibers. A defect of oxidative phosphorylation was found in both skeletal muscle and lymphocytes. It is surprising that various mtDNA deletions were detected both in the proband and in his healthy mother and maternal aunt but not in the rest of the maternal progeny. All the deletions were located between Cox II and cytochrome b genes, and short (4-5 bp) repeated sequences were consistently present at the boundaries of the rearrangements in different tissues. Therefore, the deletions appear not to be transmitted per se but to be inherited in a Mendelian manner, being possibly dominant. Both the Mendelian inheritance of the trait and the variety of the deletions in carriers suggest that a nuclearly encoded factor(s) might be involved in the triggering of the deletions. However, the presence of the rearrangements in healthy individuals raises the question of whether mtDNA deletions actually cause the clinical expression of the disease.
在一个先证者患有共济失调和酮症酸中毒昏迷的家族中发现了线粒体基因组的多处缺失。在疾病过程中出现了进行性多器官受累，组织病理学检查显示出线粒体肌病伴有破碎红纤维的特征。在骨骼肌和淋巴细胞中均发现了氧化磷酸化缺陷。令人惊讶的是，在先证者及其健康的母亲和外祖母中均检测到各种线粒体DNA缺失，但在其余的母系后代中未检测到。所有缺失均位于细胞色素氧化酶亚基II（Cox II）和细胞色素b基因之间，并且在不同组织中重排的边界处始终存在短（4 - 5个碱基对）重复序列。因此，这些缺失似乎本身不会遗传，而是以孟德尔方式遗传，可能是显性遗传。该性状的孟德尔遗传以及携带者中缺失的多样性表明，一种核编码因子可能参与了缺失的引发。然而，健康个体中存在重排这一现象引发了一个问题，即线粒体DNA缺失是否真的导致了该疾病的临床表型。
